HLA associations with occupational sensitization to rat lipocalin allergens: a model for other animal allergies?

Laboratory animal allergy is a common occupational health problem affecting between 11% and 44% of exposed researchers. Allergy to rats and mice is most common, probably because these are the animals most frequently used. We hypothesized that HLA class II molecules, involved in the presentation of allergen to the T cell and likely candidates for controlling the immune response, might be associated with sensitization to rat urinary proteins among laboratory animal handlers. We undertook a cross-sectional study of 741 employees at 6 pharmaceutical sites across the United Kingdom who had contact at work with laboratory rats. In all, 109 cases with specific sensitization to rat proteins and 397 referents were HLA-typed for DRB1 and DQB1 loci. Amino acid analyses of significantly associated HLA molecules were carried out. HLA-DR7 was associated with sensitization (odds ratio [OR], 1.82; CI, 1.12-2.97), respiratory symptoms at work (OR, 2.96; CI, 1.64-5.37) and, most strongly, sensitization with symptoms (OR, 3.81; CI, 1.90-7.65). HLA-DR3 was protective against sensitization (OR, 0.55; CI, 0.31-0.97). Amino acid analyses of these 2 molecules indicated a biologically plausible explanation for the associations. HLA phenotype is an important determinant of individual susceptibility to sensitization and asthma among laboratory animal workers. Similar mechanisms might apply in other animal allergies.